[ CAS No. 82278-73-7 ] {[proInfo.proName]}

Name: 82278-73-7|Boc-Phe(3-Br)-OH|98%
Brand: Ambeed
SKU: A155273
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Quality Control of [ 82278-73-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 82278-73-7 ]

SDS Specification

Alternatived Products of [ 82278-73-7 ]

Product Details of [ 82278-73-7 ]

CAS No. :	82278-73-7	MDL No. :	MFCD01317710
Formula :	C₁₄H₁₈BrNO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FBUDYESOPLBQIR-NSHDSACASA-N
M.W :	344.20	Pubchem ID :	2734476
Synonyms :

Calculated chemistry of [ 82278-73-7 ]

Physicochemical Properties

Num. heavy atoms :	20
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.43
Num. rotatable bonds :	7
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	79.04
TPSA :	75.63 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.12 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.23
Log Po/w (XLOGP3) :	3.21
Log Po/w (WLOGP) :	2.97
Log Po/w (MLOGP) :	2.61
Log Po/w (SILICOS-IT) :	2.34
Consensus Log Po/w :	2.67

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.76
Solubility :	0.0603 mg/ml ; 0.000175 mol/l
Class :	Soluble
Log S (Ali) :	-4.47
Solubility :	0.0117 mg/ml ; 0.0000338 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-3.99
Solubility :	0.0351 mg/ml ; 0.000102 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.92

Safety of [ 82278-73-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 82278-73-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 82278-73-7 ]
Downstream synthetic route of [ 82278-73-7 ]

[ 82278-73-7 ] Synthesis Path-Upstream 1~5

1
[ 82278-73-7 ]
[ 82311-69-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydrogenchloride In 1,4-dioxane at 20℃; for 16 h;	(2S)-3-(3-Bromophenyl)-2-(ter^butoxycarbonylamino)propionic acid (5.0 g, 14.5 mmol) was suspended in 4M HCl in 1 ,4-dioxane (75 mL) and stirred for 16 h at r.t. The white precipitate was filtered and washed with Et₂O to give the title compound (3.2 g, 89percent) as a white solid that required no further purification. δ_H (CDCl₃) 8.32 (2H, s), 7.50- 7.48 (2H, m), 7.34-7.29 (2H, m), 4.22 (IH, t, J6.2 Hz), 3.13-3.11 (2H, m).
89%	With hydrogenchloride In 1,4-dioxane at 20℃; for 16 h;	INTERMEDIATE 65 3 -Bromo-L-phenylalanine(2jS)-3-(3-Bromophenyl)-2-(tert-butoxycarbonylamino)propiomc acid (5.0 g, 14.5 mmol) was suspended in 4M HCl in 1,4-dioxane (75 mL) and stirred for 16 h at r.t.. The white precipitate was filtered and washed with Et₂O to give the title compound as a white solid (3.2 g, 89percent) that required no further purification. δ_H (CDCl₃) 8.32 (2H, s), 7.50- 7.48 (2H, m), 7.34-7.29 (2H, m), 4.22 (IH, t, J 6.2 Hz), 3.13-3.11 (2H, m). An exchangeable proton was not observed.

Reference： [1] Patent: WO2008/47109, 2008, A1, . Location in patent: Page/Page column 42
[2] Patent: WO2006/114606, 2006, A1, . Location in patent: Page/Page column 61

2
[ 24424-99-5 ]
[ 82311-69-1 ]
[ 82278-73-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydrogencarbonate In 1,4-dioxane; water	[00121] t-Butylcarbamate (Boc) protection of the amino group of bromophenylalaninewas accomplished, using sodium bicarbonate (3 equivalents), t-butyl dicarbonate (Boc2O, 1.1equivalent) in dioxane and water, to obtain compound 7 in 98percent yield. A methyl sulfone functionality was introduced by treating the bromo compound 7 with copper iodide (0.4 equivalents), cesium carbonate (0.5 equivalents), L-proline (0.8 equivalents), and the sodium salt of methanesulfinic acid (3.9 equivalents) in dimethylsulfoxide (DMSO) at 95-100°C for a totalof 9 hours, with two further additions of copper iodide (0.2 equivalents) and L-proline (0.4 equivalents) during that period. Compound 8 was isolated in 96percent yield. The carboxylic acid of compound 8 was converted to the benzyl ester, compound 9, in 99percent yield, using benzyl alcohol (1 .1 equivalent), dimethylaminopyridine (DMAP, 0.1 equivalent) and N-(3 - dimethylaminopropyl)-N-ethylcarbodiimide (EDC, 1.0 equivalent). The amino group ofcompound 9 is deprotected by adding a 4N solution of HC1 in dioxane to compound 9 at 0°C in methylene chloride. The HC1 salt of the free amino species, compound 10 was isolated in 94percent yield.

Reference： [1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 3, p. 203 - 206
[2] Patent: WO2014/18748, 2014, A1, . Location in patent: Paragraph 00120; 00121; 00122; 00123; 00124; 00125
[3] Catalysis Science and Technology, 2016, vol. 6, # 12, p. 4086 - 4089
[4] Patent: WO2009/102876, 2009, A1, . Location in patent: Page/Page column 56

3
[ 880347-42-2 ]
[ 24424-99-5 ]
[ 82278-73-7 ]

Yield	Reaction Conditions	Operation in experiment
17%	Stage #1: With sodium hydroxide In water for 2 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In 1,4-dioxane at 0 - 20℃;	C. (S)-3-(3-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid.; A suspension of 2-amino-3-(3-bromo-phenyl)-N-((2R)-hydroxy-(1R)-methyl-2-phenyl-ethyl)-N-methyl-propionamide (232 mg, 0.593 mmol) in 1 M NaOH (1.2 mL) and water (1.2 mL) was heated at reflux for 2 h and then cooled to rt, whereupon the clear solution became cloudy. Water (10 mL) was added and the solution was extracted with DCM (2.x.). The combined organic layers were washed with water. The aqueous layers were back-extracted with DCM, then combined and concentrated to 5 mL. NaHCO₃(100 mg, 1.19 mmol) and dioxane (10 mL) were added. The mixture was cooled to 0° C. and di-tert-butyl dicarbonate (0.24 mL, 1.02 mmol) was added. The reaction mixture was stirred overnight and allowed to warm to rt. Water (20 mL) was added and the solution was extracted with EtOAc (3.x.). The organic layers were combined and washed with 2percent aq. NaHCO₃. The combined aqueous layers were acidified to pH 3.5 with satd. aq. citric acid and extracted with EtOAc (3.x.). The organic layers were combined, washed with water, dried (Na₂SO₄), and concentrated to provide the product as a clear, colorless oil (38 mg, 17percent). ¹H NMR (400 MHz, CDCl₃; 1.7:1 ratio of rotamers): 7.40-7.33 (m, 3.2H), 7.12-7.20 (m, 3.2H), 6.69 (d, J=6.8, 0.6H), 5.00 (d, J=7.8, 1H), 4.62-4.54 (m, 1H), 4.48-4.34 (m, 0.6H), 3.26-3.12 (m, 1.6H), 3.10-2.84 (m, 1.6H), 1.43 (s, 9H), 1.29 (s, 5.4H).

Reference： [1] Patent: US2006/69286, 2006, A1, . Location in patent: Page/Page column 20

4
[ 14473-91-7 ]
[ 82278-73-7 ]

Reference： [1] Catalysis Science and Technology, 2016, vol. 6, # 12, p. 4086 - 4089

5
[ 82278-73-7 ]
[ 1194550-59-8 ]

Reference： [1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 3, p. 203 - 206
[2] Patent: WO2014/18748, 2014, A1,

[ 82278-73-7 ] Synthesis Path-Downstream 1~88

1
[ 82278-73-7 ]
[ 151-63-3 ]
(S)-N-(tert-butyloxycarbonyl)-(3-bromophenyl)alanylglycine nitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 7688 - 7707

2
[ 82278-73-7 ]
[2-biphenyl-3-yl-1-(cyanomethyl-carbamoyl)-ethyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 7688 - 7707

3
[ 82278-73-7 ]
[ 468740-94-5 ]

Yield	Reaction Conditions	Operation in experiment
92%		Step A tert-butyl[(1S)-1-(3-bromobenzyl)-2-hydroxyethyl]carbamate To a solution of <strong>[82278-73-7](2S)-3-(3-bromophenyl)-2-[(tert-butoxycarbonyl)amino]propanoic acid</strong> (Chem-Impex) (15 g, 44 mmol) in tetrahydrofuran (31 mL, 380 mmol) with stirring, 1.0 M borane-THF complex in THF (130 mL) was added dropwise to keep temperature at 0 C. (about 15 min). After addition the reaction mixture was stirred at room temperature for 1 h, cooled with an ice-bath, quenched with AcOH:MeOH (1:5, 70 mL), and partitioned between saturated aqueous NaHCO3 solution and DCM, dried over sodium sulfate and evaporated under reduced pressure to give 13.2 g (92% yield) of the crude desired product, which was used in the next reaction with no further purification. LC-MS found: 330.1 (M+H)+.
83%	With borane-THF; In tetrahydrofuran; at 20℃; for 14h;	General Procedure for the Preparation of 2-Amino-3- (substituted-phenyl) propanol: (S)-[2-(3-BROMO-PHENYL)-L-HYDROXYMETHYL-ETHYL]-CARBAMIC acid tert-butyl ester: To a solution of (S)-3- (3-BROMO-PHENYL)-2-TERT-BUTOXYCARBONYLAMINO-PROPINIC acid (500 mg, 1.45 mmol) in THF (30 mL) was added borane-tetrahydrofuran complex (1.0 M solution) (4.35 ML, 4.35 mmol). The reaction mixture was stirred at room temperature for 14 h and quenched with acetic acid (1 mL). After removal of most solvent, the residue was extracted with EtOAc, washed with brine, dried over NA2S04. After concentration, the crude product (400 mg, 83%) was used for the next step without purification. LCMS (M+H) + M/Z 330 (t = 1.61 min
83%	With borane-THF; In tetrahydrofuran; at 20℃; for 14h;	(S)-(2-(3-Bromo-phenyl)-1-hydroxymethyl-ethyl]-carbamic acid tert-butyl ester: To a solution of (S)-3-(3-bromo-phenyl)-2-tert-butoxycarbonylamino-propinic acid (500 mg, 1.45 mmol) in THF (30 mL) was added borane-tetrahydrofuran complex (1.0 M solution) (4.35 mL, 4.35 mmol). The reaction mixture was stirred at room temperature for 14 h and quenched with acetic acid (1 mL). After removal of most solvent, the residue was extracted with EtOAc, washed with brine, dried over Na2SO4. After concentration, the crude product (400 mg, 83%) was used the preparation of (S)-2-Amino-3-(3-bromo-phenyl)-propan-1-ol without purification. LCMS (M+H)+ m/z 330 (t=1.61 min

83%		To a solution of (S)-3-(3-bromo-phenyl)-2-tert-butoxycarbonylamino-propinic acid (500 mg, 1.45 mmol) in THF (30 mL) was added borane-tetrahydrofuran complex (1.0 M solution) (4.35 mL, 4.35 mmol). The reaction mixture was stirred at room temperature for 14 h and quenched with acetic acid (1 mL). After removal of most solvent, the residue was extracted with EtOAc, washed with brine, dried over Na2SO4. After concentration, the crude product (400 mg, 83%) was used for the next step without purification. LCMS (M+H)+m/z 330 (t=1.61 min).
83%	With borane-THF; In tetrahydrofuran; at 20℃; for 14h;	To a solution of (S)-3-(3-bromo-phenyl)-2-tert-butoxycarbonylamino-propinic acid (500 mg, 1.45 mmol) in THF (30 mL) was added borane-tetrahydrofuran complex (1.0 M solution) (4.35 mL, 4.35 mmol). The reaction mixture was stirred at room temperature for 14 h and quenched with acetic acid (1 mL). After removal of most solvent, the residue was extracted with EtOAc, washed with brine, dried over Na2SO4. After concentration, the crude product (400 mg, 83%) was used for the next step without purification. LCMS (M+H)+ m/z 330 (t=1.61 min

Reference： [1]Patent: US2013/96144,2013,A1 .Location in patent: Paragraph 0205
[2]Patent: WO2004/63151,2004,A2 .Location in patent: Page 37
[3]Patent: US2005/187218,2005,A1 .Location in patent: Page/Page column 10
[4]Patent: US2005/54655,2005,A1 .Location in patent: Page/Page column 13
[5]Patent: US2004/44203,2004,A1 .Location in patent: Page 22

4
[ 82278-73-7 ]
[ 18107-18-1 ]
[ 546115-43-9 ]

Yield	Reaction Conditions	Operation in experiment
		To an ice-cold solution of Boc-L-3-bromophenylalanine (9.44 g, 27.4 mmol) intoluene (60 ml) and MeOH (12 ml) was added 2M (trimethylsilyl) diazomethane inhexanes (20 ml). The solution was stirred at RT for 1 h and AcOH (2 ml) was added.The mixture was concentrated and the residue was dissolved in 20% MeOH/CH2CI2(40 ml). The solution was cooled in an ice-water bath and 4N HCI/dioxane (36 ml)was added via dropping funnel over 30 min. After the addition was complete, themixture was warmed to RT and stirred for 4 h. The mixture was concentrated to givethe product (8.95 g, 100%). MS m/e 258 (M+H)+

Reference： [1]Patent: WO2006/14762,2006,A1 .Location in patent: Page/Page column 36

5
[ 82278-73-7 ]
[ 82311-69-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydrogenchloride; In 1,4-dioxane; at 20℃; for 16h;	(2S)-3-(3-Bromophenyl)-2-(ter^butoxycarbonylamino)propionic acid (5.0 g, 14.5 mmol) was suspended in 4M HCl in 1 ,4-dioxane (75 mL) and stirred for 16 h at r.t. The white precipitate was filtered and washed with Et2O to give the title compound (3.2 g, 89%) as a white solid that required no further purification. deltaH (CDCl3) 8.32 (2H, s), 7.50- 7.48 (2H, m), 7.34-7.29 (2H, m), 4.22 (IH, t, J6.2 Hz), 3.13-3.11 (2H, m).
89%	With hydrogenchloride; In 1,4-dioxane; at 20℃; for 16h;	INTERMEDIATE 65 3 -Bromo-L-phenylalanine(2jS)-3-(3-Bromophenyl)-2-(tert-butoxycarbonylamino)propiomc acid (5.0 g, 14.5 mmol) was suspended in 4M HCl in 1,4-dioxane (75 mL) and stirred for 16 h at r.t.. The white precipitate was filtered and washed with Et2O to give the title compound as a white solid (3.2 g, 89%) that required no further purification. deltaH (CDCl3) 8.32 (2H, s), 7.50- 7.48 (2H, m), 7.34-7.29 (2H, m), 4.22 (IH, t, J 6.2 Hz), 3.13-3.11 (2H, m). An exchangeable proton was not observed.

Reference： [1]Patent: WO2008/47109,2008,A1 .Location in patent: Page/Page column 42
[2]Patent: WO2006/114606,2006,A1 .Location in patent: Page/Page column 61

6
[ 24424-99-5 ]
[ 82311-69-1 ]
[ 82278-73-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydrogencarbonate; In 1,4-dioxane; water;	[00121] t-Butylcarbamate (Boc) protection of the amino group of bromophenylalaninewas accomplished, using sodium bicarbonate (3 equivalents), t-butyl dicarbonate (Boc2O, 1.1equivalent) in dioxane and water, to obtain compound 7 in 98% yield. A methyl sulfone functionality was introduced by treating the bromo compound 7 with copper iodide (0.4 equivalents), cesium carbonate (0.5 equivalents), L-proline (0.8 equivalents), and the sodium salt of methanesulfinic acid (3.9 equivalents) in dimethylsulfoxide (DMSO) at 95-100C for a totalof 9 hours, with two further additions of copper iodide (0.2 equivalents) and L-proline (0.4 equivalents) during that period. Compound 8 was isolated in 96% yield. The carboxylic acid of compound 8 was converted to the benzyl ester, compound 9, in 99% yield, using benzyl alcohol (1 .1 equivalent), dimethylaminopyridine (DMAP, 0.1 equivalent) and N-(3 - dimethylaminopropyl)-N-ethylcarbodiimide (EDC, 1.0 equivalent). The amino group ofcompound 9 is deprotected by adding a 4N solution of HC1 in dioxane to compound 9 at 0C in methylene chloride. The HC1 salt of the free amino species, compound 10 was isolated in 94% yield.
	With triethylamine; In methanol; at 20℃;	To a solution of L-3-Bromophenylalanine (0.6 g, 2.47 mmol) in CH3OH (20 ml) was added (Boc)2O (0.6 g, 2.72 mmol) and NEt3 (1.49 g, 4.94 mmol) The resulting mixture was stirred at room temperature overnight. Solvents were removed under reduced pressure and the residue was dissolved in EtOAc (30 mL). The solution was washed with IN HCl (10 mL), brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated to afford crude compound 15 which was used in the next step without further purification.

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1 .Location in patent: Paragraph 00120; 00121; 00122; 00123; 00124; 00125
[3]Catalysis science and technology,2016,vol. 6,p. 4086 - 4089
[4]Patent: WO2009/102876,2009,A1 .Location in patent: Page/Page column 56

7
(1R,2S)-1-amino-2-vinylcyclopropane carboxylic acid methyl ester tosylate salt [ No CAS ]
[ 82278-73-7 ]
C₂₁H₂₇BrN₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃;	To a solution of compound 15 (0.84 g, 2.44 mmol) in DCM (10 mL) was added HATU (1.21 g, 3.17 mmol). On a separate flask, to a solution of (1R,2S)- Amino-2-Vinylcyclopropane-OMe-pTSA (0.84 g, 2.68 mmol) in DCM (10 ml) was added DIPEA (0.81 ml, 4.88 mmol). This second solution was added to the first one containing compound 1 and the resulting mixture was stirred at room temperature overnight. The reaction solution was diluted with DCM (40 mL), washed with saturated NaHCO3 (15 mL) and brine (15 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. After purification by silica gel column chromatography, 0.7 g of compound 16 were obtained with (61% yield).

Reference： [1]Patent: WO2009/102876,2009,A1 .Location in patent: Page/Page column 57

8
[ 880347-42-2 ]
[ 24424-99-5 ]
[ 82278-73-7 ]

Yield	Reaction Conditions	Operation in experiment
17%		C. (S)-3-(3-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid.; A suspension of 2-amino-3-(3-bromo-phenyl)-N-((2R)-hydroxy-(1R)-methyl-2-phenyl-ethyl)-N-methyl-propionamide (232 mg, 0.593 mmol) in 1 M NaOH (1.2 mL) and water (1.2 mL) was heated at reflux for 2 h and then cooled to rt, whereupon the clear solution became cloudy. Water (10 mL) was added and the solution was extracted with DCM (2×). The combined organic layers were washed with water. The aqueous layers were back-extracted with DCM, then combined and concentrated to 5 mL. NaHCO3 (100 mg, 1.19 mmol) and dioxane (10 mL) were added. The mixture was cooled to 0 C. and di-tert-butyl dicarbonate (0.24 mL, 1.02 mmol) was added. The reaction mixture was stirred overnight and allowed to warm to rt. Water (20 mL) was added and the solution was extracted with EtOAc (3×). The organic layers were combined and washed with 2% aq. NaHCO3. The combined aqueous layers were acidified to pH 3.5 with satd. aq. citric acid and extracted with EtOAc (3×). The organic layers were combined, washed with water, dried (Na2SO4), and concentrated to provide the product as a clear, colorless oil (38 mg, 17%). 1H NMR (400 MHz, CDCl3; 1.7:1 ratio of rotamers): 7.40-7.33 (m, 3.2H), 7.12-7.20 (m, 3.2H), 6.69 (d, J=6.8, 0.6H), 5.00 (d, J=7.8, 1H), 4.62-4.54 (m, 1H), 4.48-4.34 (m, 0.6H), 3.26-3.12 (m, 1.6H), 3.10-2.84 (m, 1.6H), 1.43 (s, 9H), 1.29 (s, 5.4H).

Reference： [1]Patent: US2006/69286,2006,A1 .Location in patent: Page/Page column 20

9
[ 82278-73-7 ]
[ 74-88-4 ]
[ 546115-43-9 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3870 - 3873

10
[ 82278-73-7 ]
[ 1192344-14-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6390 - 6401

11
[ 82278-73-7 ]
[ 1192344-35-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6390 - 6401

12
[ 82278-73-7 ]
[ 75-03-6 ]
[ 1159502-91-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6390 - 6401
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 448 - 461

13
[ 82278-73-7 ]
[ 1289646-78-1 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1

14
[ 82278-73-7 ]
[ 1194550-59-8 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1

15
[ 82278-73-7 ]
[ 1194550-63-4 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1

16
[ 82278-73-7 ]
[ 1194550-65-6 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1
[3]Patent: WO2014/18748,2014,A1

17
[ 82278-73-7 ]
[ 1194550-67-8 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206
[2]Patent: WO2014/18748,2014,A1
[3]Patent: WO2014/18748,2014,A1

18
[ 82278-73-7 ]
[ 20277-69-4 ]
[ 1289646-76-9 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 203 - 206

19
[ 82278-73-7 ]
aminomethyl-terminated Tentagel resin [ No CAS ]
[ 15761-38-3 ]
(S)-2-acetamido-3-(3-boronophenyl)-2-methylpropanoic acid [ No CAS ]
[ 108-24-7 ]
C₃₁H₄₁BBrN₆O₈Pol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3099 - 3114

20
[ 82278-73-7 ]
aminomethyl-terminated Tentagel resin [ No CAS ]
[ 15761-38-3 ]
[ 30992-29-1 ]
[ 1364705-24-7 ]
[ 108-24-7 ]
C₃₇H₅₀BBrClN₆O₈Pol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3099 - 3114

21
[ 82278-73-7 ]
aminomethyl-terminated Tentagel resin [ No CAS ]
[ 15761-38-3 ]
[ 30992-29-1 ]
[ 1364705-24-7 ]
[ 108-24-7 ]
C₃₇H₅₀BBrClN₆O₈Pol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3099 - 3114

22
[ 82278-73-7 ]
aminomethyl-terminated Tentagel resin [ No CAS ]
[ 15761-38-3 ]
[ 30992-29-1 ]
[ 1364705-24-7 ]
[ 108-24-7 ]
C₃₇H₅₀BBrClN₆O₈Pol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3099 - 3114

23
[ 82278-73-7 ]
aminomethyl-terminated Tentagel resin [ No CAS ]
[ 15761-38-3 ]
[ 1364705-24-7 ]
[ 108-24-7 ]
C₃₆H₄₈BBrClN₆O₈Pol [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 3099 - 3114

24
[ 82278-73-7 ]
[ 1430058-03-9 ]

Reference： [1]Patent: US2013/96144,2013,A1

25
[ 82278-73-7 ]
[2-(3-cyano-phenyl)-1-hydroxymethyl-ethyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]

Reference： [1]Patent: US2013/96144,2013,A1

26
[ 82278-73-7 ]
[ 1430057-96-7 ]

Reference： [1]Patent: US2013/96144,2013,A1

27
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[ 1194550-61-2 ]

Reference： [1]Patent: WO2014/18748,2014,A1

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[ 67-71-0 ]
[ 1289646-76-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With copper(l) iodide; sodium methansulfinate; caesium carbonate; L-proline; In dimethyl sulfoxide; at 95 - 100℃; for 9h;	[00121] t-Butylcarbamate (Boc) protection of the amino group of bromophenylalaninewas accomplished, using sodium bicarbonate (3 equivalents), t-butyl dicarbonate (Boc2O, 1.1equivalent) in dioxane and water, to obtain compound 7 in 98% yield. A methyl sulfone functionality was introduced by treating the bromo compound 7 with copper iodide (0.4 equivalents), cesium carbonate (0.5 equivalents), L-proline (0.8 equivalents), and the sodium salt of methanesulfinic acid (3.9 equivalents) in dimethylsulfoxide (DMSO) at 95-100C for a totalof 9 hours, with two further additions of copper iodide (0.2 equivalents) and L-proline (0.4 equivalents) during that period. Compound 8 was isolated in 96% yield. The carboxylic acid of compound 8 was converted to the benzyl ester, compound 9, in 99% yield, using benzyl alcohol (1 .1 equivalent), dimethylaminopyridine (DMAP, 0.1 equivalent) and N-(3 - dimethylaminopropyl)-N-ethylcarbodiimide (EDC, 1.0 equivalent). The amino group ofcompound 9 is deprotected by adding a 4N solution of HC1 in dioxane to compound 9 at 0C in methylene chloride. The HC1 salt of the free amino species, compound 10 was isolated in 94% yield.

Reference： [1]Patent: WO2014/18748,2014,A1 .Location in patent: Paragraph 00120; 00121; 00122; 00123; 00124; 00125

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C₃₄H₃₇ClN₄O₅ [ No CAS ]